Interest in the identification of cysteine sulfenic acids (R—SOH) in proteins by biochemists has grown substantially over the last decade as their biological roles in redox regulation and catalysis within an array of cellular proteins have become better defined (1,2). In spite of their importance, only a limited set of tools to identify these species are available, and most of these are only applicable to in vitro studies of pure, isolated proteins (3,4). Chemical modification of cysteine sulfenic acids by dimedone (5,5-dimethyl-1,3-cyclohexanedione) provides a useful way to “tag” these species with a specific, irreversible alkylating agent, but the lack of any spectral signal or label associated with the dimedone requires that the detection of this tag be undertaken by mass spectrometry (4-7).